ATLANTA, Dec. 12 /PRNewswire-FirstCall/ -- Laboratory findings demonstrate that the anti-cancer compound CEP-701 (lestaurtinib) inhibits a specific genetic mutation targeted by the compound in patients’ blood samples and were predictive of a positive clinical response, according to preliminary data from a Phase 2 study of patients with acute myelogenous leukemia (AML) who bear a FLT3 activating mutation at first relapse from standard induction chemotherapy. The early data suggest that chemotherapy followed by the oral compound CEP-701 may offer a clinical benefit compared to chemotherapy alone. Preliminary results of this ongoing, randomized multi-center trial sponsored by Cephalon Oncology were announced in a platform presentation at the 47th Annual Meeting of the American Society of Hematology (ASH) today.
CEP-701 is under development by Cephalon, Inc. as a treatment for FLT3-mutated AML, a hematologic cancer characterized by uncontrolled growth of myeloid cells of the blood and bone marrow. According to the American Cancer Society, an estimated 12,000 people in the United States will be diagnosed with AML in 2005. Approximately 25-30 percent of AML patients have a FLT3 genetic mutation that is associated with a poorer prognosis for relapse and survival. CEP-701 is a novel oral indolocarbazole agent that inhibits the receptor tyrosine kinase FLT3.
To date, forty-four patients have been randomly assigned to one of two treatment arms in the clinical trial: standard chemotherapy alone, or chemotherapy followed 2 days later by a daily 80-mg orally administered dose of CEP-701, continued for up to 113 days. The data presented suggest that the addition of CEP-701 enhances the complete remission rate. Ten of 22 patients (45 percent) in the arm receiving chemotherapy followed by CEP-701 achieved a complete response, compared with six of 22 (27 percent) treated with chemotherapy alone.
In addition, the study is assessing the relationship of clinical response rate to the baseline cell sensitivity to CEP-701 as assessed by an in vitro cytotoxic assay, and FLT3 inhibition as measured ex vivo from blood samples after treatment. To date, a clinical response has been achieved in all patients who showed an 85 percent or greater inhibition of FLT3 activity and baseline cellular sensitivity to CEP-701. Patients with low FLT3-inhibitory activity or cells insensitive to CEP-701 had a very low rate of clinical response. These data suggest that there is potential to predict which patients will respond positively to CEP-701.
Preliminary safety analyses indicate that CEP-701 is generally well tolerated, with only a modest increase in gastrointestinal events such as nausea and dyspepsia reported. However, these side effects rarely resulted in discontinuation from the study.
“Therapies that target FLT3 and other important genetic mutations may allow us to better manage diseases with a poor prognosis,” said Mark Levis, M.D., Ph.D., a study investigator and Assistant Professor of Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore. “The ability to correlate molecular activity with clinical response in this patient population is an important step in demonstrating that CEP-701 acts as a targeted biotherapy.”
This study is ongoing; for more information, visit http://www.clinicaltrials.gov.
“Based on the growing body of data, we believe CEP-701 has the potential to provide additional clinical benefit to that seen with chemotherapy alone in this group of patients with AML at time of first relapse,” said Dr. Lesley Russell, Cephalon’s Senior Vice President, Worldwide Clinical Research. “Cephalon Oncology is committed to further development of CEP-701 in AML and the evaluation of other indications where its oncogenic targets are expressed.”
Researchers at ASH will report details at a platform presentation of the ongoing study of CEP-701 in FLT3-mutated AML:
-- A Randomized, Open-Label Study of Lestaurtinib (CEP-701), an Oral FLT3 Inhibitor, Administered in Sequence with Chemotherapy in Patients with Relapsed AML Harboring FLT3 Activating Mutations: Clinical Response Correlates with Successful FLT3 Inhibition. Levis, et.al., Abstract 403, Monday, December 12, 1:30 p.m. EST. Location: Thomas Murphy 4 Cephalon Oncology Portfolio
The Cephalon Oncology portfolio includes three lead compounds to treat patients with hematologic cancers: TRISENOX(R) (arsenic trioxide) injection, an intravenous arsenic-based targeted therapy; TREANDA(R) (bendamustine HCl), a multi-functional hybrid cytotoxic; and CEP-701, an oral small molecule tyrosine kinase inhibitor.
TRISENOX is indicated for the induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression. Full prescribing information, including boxed warning, is available at http://www.trisenox.com. TRISENOX is not presently indicated or approved by the Food and Drug Administration (FDA) for use in any other disease or related cancer.
TREANDA and CEP-701 are investigational agents under active clinical development for relapsed indolent non-Hodgkin’s lymphoma and acute myelogenous leukemia associated with mutations on the kinase FLT3, respectively; neither compound is presently indicated or approved by the FDA for these or any other diseases.
For more information about Cephalon Oncology, visit http://www.cephalononcology.com.
Cephalon, Inc.
Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products to treat sleep and neurological disorders, cancer and pain. Cephalon currently employs approximately 2,500 people in the United States and Europe. U.S. sites include the company’s headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. Cephalon’s European headquarters are located in Maisons-Alfort, France and other European offices are located in Guildford, England, and Martinsried, Germany.
The company currently markets four proprietary products in the United States: PROVIGIL(R) (modafinil) [C-IV], GABITRIL(R) (tiagabine hydrochloride), ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II] and TRISENOX and more than 20 products internationally. Full prescribing information on its U.S. products is available at http://www.cephalon.com or by calling 1-800-896-5855
In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon’s current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential pharmaceutical products, including TREANDA and CEP-701, interpretation of clinical results, prospects for regulatory approval of our product candidates, manufacturing development and capabilities, market prospects for its products, including prospects deriving from Cephalon’s commercial presence in the oncology market or otherwise as a result of building a fully integrated oncology business, sales and earnings guidance, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as “anticipate,” “estimate,” “expect,” “project,” “intend,” “plan,” “believe” or other words and terms of similar meaning. Cephalon’s performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion.
Cephalon, Inc.
CONTACT: Media: Stacey Beckhardt, +1-610-738-6198 office, or+1-610-247-0212 mobile, or sbeckhar@cephalon.com, or Investors: Robert(Chip) Merritt, +1-610-738-6376, cmerritt@cephalon.com, both of Cephalon,Inc.
Company News On-Call: http://www.prnewswire.com/comp/134563.html/
